Abstract: This translational research endeavor employed an established cue reactivity methodology in humans to provide the first evidence of the therapeutic potential of an untested and potentially promising adjunctive pharmacotherapy for one of the most prevalent and intractable mental health comorbidities, PTSD and alcohol dependence.

Supporting Summary:

Aims: Memories for both aversive and appetitive learning can be retrieved by presentation of cues associated with those memories. According to the reconsolidation hypothesis, retrieved memories enter a labile state prior to being restabilized in long-term storage, a process referred to as reconsolidation. During this period of lability, the memories may be pharmacologically altered or attenuated. Modulation of reconsolidation can lead to diminution or elimination of behavior(s) originally supported by the learning. We recently completed a laboratory study of a novel medication intervention that targeted attenuation of trauma related distress by altering trauma memory reconsolidation in individuals with PTSD and comorbid alcohol dependence (AD). The medication intervention consisted of the administration of the β-blocking agent, propranolol, immediately following the presentation trauma cues (the cues initiate the reconsolidation). A placebo control group was treated identically with the exception that they received inactive placebo following retrieval. In a test session performed the next day, we examined subjective distress and alcohol craving to both trauma and alcohol cues. It was hypothesized that propranolol-treated PTSD+AD individuals would evidence lower distress and craving during the test session than placebo-treated individuals. Methods: PTSD+AD participants received either 40 mg propranolol (n=21) or placebo (n=23) immediately following trauma cue exposure (description of participant’s worst trauma presented via headphones). After remaining overnight in an alcohol-free environment, participants received a ‘test’ session of cue exposure that was identical to the first session except (a) trauma cue exposure was followed by alcohol cue exposure, and (b) no medication was administered. Subjective distress and craving were measured (100 point scale) prior to, during, and following cue exposure in both sessions. Results: Groups did not differ on any demographic or pre-study measure of alcohol use; Group differences on depression and psychiatric symptom measures were controlled in the analyses. Compared to placebo-treated participants (= 56.0, se= 3.7), propranolol-treated (= 42.8, se= 4.0) participants evidenced significantly lower distress to the combined trauma-alcohol cues presented during the test session (p= .03). Additionally, measures of depressed mood, frustration, worry/anxiety and anger/hostility were lower in propranolol- vs. placebo-treated individuals. The groups did not evidence any difference in craving. Conclusions: This study provides the first evidence that propranolol administration following trauma cue exposure may modulate trauma memories in PTSD+AD humans. The results are consistent with the reconsolidation hypothesis and inconsistent with an alternative ‘facilitated extinction’ account since propranolol generally retards or has no effect on extinction. The present findings suggest that the targeting of both trauma- and alcohol-related cues may be a more effective strategy for employing propranolol-induced memory modulation in PTSD+AD comorbid individuals. Optimism about this dual cue approach is encouraged by our recent finding that post-retrieval propranolol attenuates cue elicited craving in cocaine dependent individuals (Saladin et al, 2013).

Financial Support: This research was supported by NIAAA grant 5RC1AA019019 (M. E. Saladin, PI), USPHS grant M01 RR01070 (CTRC, MUSC) and by the South Carolina Clinical & Translational Research (SCTR) Institute, with an academic home at MUSC, through NIH Grant Numbers UL1 RR029882 and UL1 TR000062.